The invention relates to a flexible platform or plate holder for use with liquid handling robots. More specifically the invention relates to a flexible platform for use with a variety of plate holders which allows for complete removal of a sample from a well without the need for liquid sensors and for the addition of small volumes without creating bubbles.
Liquid handling robots are the cornerstones of modem automated biological laboratories. Yet, while they make some tasks much easier to accomplish than manual methods, there are still some tasks that are beyond the capabilities of current instrumentation. Most of these limitations involve processes that normally require the sensitive touch of a human being. For example, such processes include the ability to manipulate the tip of a pipetman to the bottom of a tube or well and to extract all or nearly all of the liquid within that tube. Another example is the ability to add a small volume of liquid to a tube or well without creating a bubble or bubbles. This is very important in biological reactions, as they are typically carried out in a very small volume, typically in the range of 1-100 xcexcl, but with an increasing trend towards even smaller volumes in the nanoliter and picoliter range. Under these conditions, bubbles or any variance in the concentration of the components can lead to detrimental results. Thus, if the sample is involved in a number of different reactions within the same tube or well of a plate, it is important to include a washing step and a drying step. The final drying step should ideally eliminate all residual volume in the well, so that the next reaction is not diluted. One can imagine that if a typical reaction occurs in a total volume of 20 xcexcl and 5 xcexcl are left after the previous step, this is a significant contaminant or dilution.
Current instrumentation is very precise, but not flexible. Thus, current robots cannot account for slight plate-to-plate size or shape variations or even well-to-well size or shape variations within a plate. Variation in the seating of disposable pipette tips on the liquid handler can also pose positional problems for the robot. Although robots can be programmed such that the arm will go to an exact fixed location in space, they cannot be programmed to go to the bottom of a well, particularly if there is variation in the distance. In addition, with current automation, there is no way to apply a controlled amount of pressure between the robot arm and a plate. So, if one tries to program the robot arm to go to the bottom of a well and aspirate, it may leave a residual volume at the bottom of the well if the tip is too high (which can vary tremendously in the context of the small total volumes involved), or it may collide the tips of the robot into the bottom of the well which may damage the experiment and/or the robot (and prevent aspiration).
Various methods and apparati have been envisioned or developed as alternative solutions to this problem. For example, pipet tips which include liquid sensors have been developed. However, these tips are very expensive and may necessitate the purchase of one or more further apparati for allowing the detection. In addition, these sensing tips do not work reproducibly with small volumes. An alternative is to make the arm of the liquid handler flexible. However, this may require each manufacturer to separately re-engineer the arm of the machine, a very expensive process.
Thus a method is needed which is inexpensive and will allow for a means of controlling for variations in the height of wells or plates and will be applicable to a variety of automated handlers from different manufacturers.
One embodiment of the present invention is a platform for a liquid-handling robot having at least one robot nozzle for transferring or treating a liquid sample in a sample holder by moving upward and downward, the platform having a sample platform for receiving the sample holder; an adapter platform for fitting onto the liquid-handling robot; and a moveable connector elastically connecting the sample platform and the adapter platform, wherein elasticity of the connector is adjusted to be lower than the force of the downward movement of the nozzle to elastically lower the sample platform when the nozzle pushes the sample holder downward.
In one embodiment, the platform is configured to receive sample holders such as microtiter plates, PCR plates, microarrays, and microfluidic plates.
In a further embodiment, the platform also has chamfers for attachment of the sample holder. In a further embodiment, the platform also has a bumper between the sample platform and the adapter platform to prevent contacting each other.
In one embodiment, the moveable connector has at least one coil spring and at least one support arranged within the coil spring. Typically the support is selected from the group consisting of a screw, a pin, a nail, and a rod.
In a further embodiment, the platform also has a washer.
In a further embodiment, the sample platform and/or the adapter is manufactured of a material which is chemically inert and thermally resistant, such as a plastic.
In one embodiment, the sample platform has at least one adapter pin for positioning the adapter platform in the liquid handling robot.
A further embodiment is a platform for a liquid-handling robot having (i) a detachable sample holder having at least one well or groove for a liquid sample; (ii) an adapter for receiving the platform; and (iii) at least one robot nozzle for transferring or treating the sample in the well by moving upward and downward, the platform having: (a) an upper surface configured to contact a bottom of the sample holder, (b) a bottom surface configured to contact an upper surface of the adapter, and (c) a mechanism elastically moveable in a direction of movement of the nozzle, wherein elasticity of said platform is adjusted to be lower than the force of the downward movement of the nozzle. In one embodiment of the sample platform, the upper surface of the platform is configured to receive a sample holder selected from the group consisting of microtiter plates, PCR plates, microarrays, and microfluidic plates.
In a further embodiment, the upper surface of the platform is an upper surface of a sample platform, the bottom surface of the platform is a bottom surface of an adapter platform, and the moveable mechanism is constituted between the sample platform and the adapter platform. The moveable mechanism may be a connector and a spring. And the connector may be a screw, a pin, a nail, and a rod.
In a further embodiment, the platform also has at least one bumper for preventing the sample platform and the adapter platform from contacting each other.
A further embodiment is a method for adapting an automated liquid handler, by attaching the platform described above to an automated liquid handler to allow for variations in plate and well-size.
A further embodiment is a method for the complete aspiration of small volumes by a liquid plate handler, comprising attaching the platform described above to an automated liquid handler.
A further embodiment is a method for transfer of small volumes by an automated liquid handler, comprising attaching the platform of claim 1 to an automated liquid handler.
A further embodiment is a method for perfecting the function of microarray spotters, comprising attaching the platform of claim 1 to an automated liquid handler.
A further embodiment is a platform for any type of liquid handling robot, which has a sample platform; an adaptor platform which fits onto the liquid handling robots; and a moveable connector which allows motion on one axis between the two platforms.
In one embodiment, the sample platform allows for attachment of a sample adapter. In a further embodiment, the sample platform allows attachment of a sample holder selected from the group consisting of: microwell plates, pcr plates, microarrays, and microfluidic plates. The platform may also contain chamfers for attachment of a sample holder. In a further embodiment, the platform may contain a bumper to keep the sample platform from contacting the adaptor platform. The movable connector may be a connector and a spring. The connector may be a screw, a pin, a nail, or a rod, preferably a shoulder screw.
In one embodiment, the sample platform and or adaptor is manufactured of a material which is inert. In a further embodiment, the sample platform further comprises helicoils to allow for better attachment of the screws or pins.